System for delivering conformal radiation therapy while simultaneously imaging soft tissue

ABSTRACT

A device and a process for performing high temporal- and spatial-resolution MR imaging of the anatomy of a patient during intensity modulated radiation therapy (IMRT) to directly measure and control the highly conformal ionizing radiation dose delivered to the patient for the treatment of diseases caused by proliferative tissue disorders. This invention combines the technologies of open MRI, multileaf-collimator or compensating filter-based IMRT delivery, and cobalt teletherapy into a single co-registered and gantry mounted system.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation application of U.S. application Ser.No. 12/609,953 which was filed on Oct. 30, 2009 which is a continuationapplication of U.S. application Ser. No. 11/059,914 which was filed Feb.17, 2005, which claims the benefit of Provisional application of60/546,670 filed on Feb. 20, 2004, the entirety of which areincorporated by reference herein.

FIELD OF THE INVENTION

This invention relates to a radiotherapy system and method, moreparticularly a radiotherapy system and method for rapidly and repeatedlyimaging the anatomy of a patient during the moments that dose isdelivered to the patient during radiation therapy so that the actualionizing radiation dose delivered to the patient in portions over acourse of many days or weeks may be determined and the therapy may beadjusted to account for any treatment delivery errors caused by organmotions or changes in patient geometry. The magnetic resonance imagingmethod employed in this invention also improves the soft tissue contrastover the existing x-ray computed tomography (CT) imaging and may provideadditional metabolic and physiological information to improve targetdelineation and allow for the monitoring of the response of the patientor disease to therapy.

BACKGROUND OF THE INVENTION

In treating disease caused by proliferative tissue disorders such ascancer and coronary artery restenosis with radiation, the portions ofthe patient known to contain or suspected to contain disease areirradiated. For this purpose, a radiotherapy planning system is used tofirst acquire planning images of the diseased portion(s) and surroundingregions.

Radiotherapy planning systems generally include a CT or magneticresonance imaging (MRI) simulator. CT or MRI radiography is carried outon a single day before the beginning of therapy to acquire a pluralityof coregistered sectional 2-D images. These sectional images arecombined using known algorithms to produce 3-D images. These 3-Dsimulation images are displayed and then analyzed to identify thelocation of regions of suspected disease to be treated, such as aradiographically evident tumor or regions suspected of microscopicdisease spread. These regions to be treated are called radiotherapytargets. In order to attempt to account for organ motions, the conceptof margins and planning target volumes (PTVs) was developed to attemptto irradiate a volume that would hopefully contain the target duringmost of the irradiation. PTVs include a geometric margin to account forvariations in patient geometry or motion. Likewise, the 3-D simulationimages are displayed and then analyzed to identify important normalanatomy and tissues that may be damaged by the radiation, such as thespinal cord and lung, to evaluate the potential impact of radiation onthe function of these tissues. These regions to be spared or protectedfrom excessive radiation are called critical structures or organs atrisk and may also include a margin to account for variations in patientgeometry or motion. The delivery of radiation therapy is thentraditionally planned on a single static model of radiotherapy targetsand critical structures derived from a single set of CT and/or MRIimages. Because the known art does not allow for simultaneous imagingand therapy, the patient and all of their internal organs need to berepositioned exactly for accurate dose delivery. However, it is known inthe art that exactly repositioning the patient even for a singledelivery of dose is not possible due to several factors including: theinability to reproduce the patient setup, i.e., the geometry andalignment of the patient's body; physiological changes in the patient,such as weight loss or tumor growth and shrinkage; and organ motions inthe patients including but not limited to breathing motion, cardiacmotion, rectal distension, peristalsis, bladder filling, and voluntarymuscular motion. Note that the organ motions may occur on rapid timescales such that changes may occur during a single dose delivery (e.g.,breathing motion), termed “intra-fraction” organ motions, or they mayoccur on slower time scales such that changes occur in between dosedeliveries, termed “inter-fraction” organ motions. Much of the curativetreatment of patients with cancer outside the cranium requires thedelivered radiation therapy to be fractionated, i.e., the dose isdelivered in many fractions. Typically, dose is delivered in single 1.8to 2.2 Gy fractions or double 1.2 to 1.5 Gy fractions daily, anddelivered during the work week (Monday through Friday); taking 7 to 8weeks to deliver, e.g., a cumulative dose of 70 to 72 Gy at 2.0 or 1.8Gy, respectively. A purpose of this invention is to overcome thelimitations imposed on radiation therapy by patient setup errors,physiological changes, and both intra- and inter-fraction organ motionsthroughout the many weeks of radiation therapy. Another purpose is toallow the physician to periodically monitor the response of thepatient's disease to the therapy by performing MRI that providesmetabolic and physiological information or assessing the growth orshrinkage of gross disease.

An irradiation field shape is then determined to coincide with anoutline of an image of the target's diseased regions or suspectedregions appearing in the planning images. An irradiating angle isdetermined from sectional images of a wide region including the diseasedportion or a transmitted image, seen from a particular direction,produced by the 3-D simulation images. A transmitted image seen from theirradiating angle is displayed. The operator then determines a shape ofan irradiation field on the image displayed, and sets an isocenter(reference point) to the irradiation field.

Optionally, the patient may be positioned relative to a conventionalsimulator (ortho-voltage X-ray imaging system that allows portal imagesto be generated for radiation therapy setup). An irradiating anglecorresponding to the irradiating angle determined as above is set to thesimulator, and an image is generally radiographed on a film throughradiography for use as a reference radiograph. Similar digitallyreconstructed radiographs may be produced using CT or MRI simulationsoftware.

The patient is then positioned and restrained relative to a radiationtreating apparatus which generally includes a radiation source,typically a linear accelerator. An irradiating angle is set to theirradiating angle determined as above, and film radiography is carriedout by emitting radiation from the radiation treating apparatus. Thisradiation film image is correlated with the above film image acting asthe reference radiograph to confirm that the patient has been positionedaccording to plan as correctly as possible before proceeding withradiotherapy. Some repositioning is generally required to place thepatient such that the structures in the reference radiograph match thestructures in the treatment radiograph to within a tolerance of 0.2 to0.5 cm. After acceptable patient positioning is confirmed, radiotherapyis begun.

Patient setup errors, physiological changes, and organ motions result inincreasing misalignment of the treatment beams relative to theradiotherapy targets and critical structures of a patient as theradiotherapy process proceeds. For years practitioners have beenacquiring hard-copy films of the patient using the radiation therapybeam, technically referred to as a “port film” to attempt to ensure thatthe beam position does not significantly vary from the original plan.However, the port films acquired are generally only single 2-Dprojection images taken at some predetermined interval during theradiotherapy process (typically 1 week). Port films cannot account fororgan motion. Additionally, port films do not image soft tissue anatomywith any significant contrast and only provide reliable information onthe boney anatomy of the patient. Accordingly, misalignment informationis only provided at the instants in time in which the port images aretaken and may be misleading as the boney anatomy and soft tissue anatomyalignment need not correlate and change with time. With appropriatemarkers in the port image provided, the beam misalignment may bedetermined and then corrected to some limited degree.

More recently, some have disclosed acquiring the port imageselectronically, referred to as electronic portal imaging. This imagingtechnique employs solid state semiconductor, scintillator, or liquidionization chamber array technology to capture x-ray transmissionradiographs of the patient using the x-rays of the linear accelerator oran associated kilovoltage x-ray unit. As with the hard-copy technique,misalignment data is only provided at the instants in time in which theport images are taken. Another recent advance in electronic portalimaging includes the use of implanted interstitial radio-opaque markersthat attempt to image the location of soft tissues. These procedures areinvasive and subject to marker migration. Even when performed with therapid acquisition of many images, it only finds the motion of discretepoints identified by the radio-opaque markers inside a soft tissue andcannot account for the true complexities of organ motions and thedosimetric errors that they cause. Another recent advance, that creates3D volumetric image sets from many 2D electronic portal images, is theacquisition of volumetric cone-beam x-ray CT or helical tomotherapymegavoltage x-ray CT image set before or after the daily delivery oftherapy. While this technology may account for patient setup errors,i.e., the geometry and alignment of the patient's body, physiologicalchanges in the patient, such as weight loss or tumor growth andshrinkage, and inter-fraction organ motions in the patient, such asrectal filling and voiding; it cannot account for intra-fraction organmotions in the patients. Intrafraction organ motions are very importantand include, but are not limited to, breathing motion, cardiac motion,rectal gas distension, peristalsis, bladder filling, and voluntarymuscular motion.

Radiation therapy has historically been delivered to large regions ofthe body including the target volume. While some volume margin isrequired to account for the possibility of microscopic disease spread,much of the margin is required to account for uncertainties in treatmentplanning and delivery of radiation. Reducing the total volume of tissueirradiated is beneficial, since this reduces the amount of normal tissueirradiated and therefore reduces the overall toxicity to the patientfrom radiation therapy. Furthermore, reduction in overall treatmentvolume may allow dose escalation to the target, thus increasing theprobability of tumor control.

Clinical cobalt (Co⁶⁰ radioisotope source) therapy units and MV linearaccelerators (or linacs) were introduced nearly contemporaneously in theearly 1950's. The first two clinical cobalt therapy units were installednearly simultaneously in October of 1951 in Saskatoon and London,Ontario. The first MV linear accelerator installed solely for clinicaluse was at Hammersmith Hospital, London England in June of 1952. Thefirst patient was treated with this machine in August of 1953. Thesedevices soon became widely employed in cancer therapy. The deeplypenetrating ionizing photon beams quickly became the mainstay ofradiation therapy, allowing the widespread noninvasive treatment of deepseated tumors. The role of X-ray therapy slowly changed with the adventof these devices from a mainly palliative therapy to a definitivecurative therapy. Despite similarities, cobalt units and linacs werealways viewed as rival technologies in external beam radiotherapy. Thisrivalry would result in the eventual dominance of linacs in the UnitedStates and Western Europe. The cobalt unit was quite simplistic and wasnot technically improved significantly over time. Of course, thesimplicity of the cobalt unit was a cause for some of its appeal; thecobalt units were very reliable, precise, and required littlemaintenance and technical expertise to run. Early on, this allowedcobalt therapy to become the most widespread form of external beamtherapy. The linac was the more technically intensive device.Accelerating high currents of electrons to energies between 4 and 25 MeVto produce beams of bremsstrahlung photons or scattered electrons, thelinac was a much more versatile machine that allowed more penetratingbeams with sharper penumbrae and higher dose rates. As the linac becamemore reliable, the benefits of having more penetrating photon beamscoupled with the addition of electron beams was seen as strong enoughimpetus to replace the existing cobalt units. Cobalt therapy did not dieaway without some protests and the essence of this debate was capturedin a famous paper in 1986 by Laughlin, Mohan, and Kutcher whichexplained the pros and cons of cobalt units with linacs. This wasaccompanied by an editorial from Suit that pleaded for the continuanceand further technical development of cobalt units. The pros of cobaltunits and linacs have already been listed. The cons of cobalt units wereseen as less penetrating depth dose, larger penumbra due to source size,large surface doses for large fields due to lower energy contaminationelectrons, and mandatory regulatory oversight. The cons for linacsincreased with their increasing energy (and hence their difference froma low energy cobalt beam), and were seen to be increased builddown,increased penumbra due to electron transport, increased dose to bone(due to increased dose due to pair production), and most importantly theproduction of photo-neutrons at acceleration potentials over 10 MV.

In the era before intensity modulated radiation therapy (IMRT), thelinac held definite advantages over cobalt therapy. The fact that onecould produce a very similar beam to cobalt using a 4 MV linacaccelerating potential combined with the linac's ability to produceeither electron beams or more penetrating photon beams made the linacpreferable. When the value of cobalt therapy was being weighed againstthe value linac therapy, radiation fields were only manually developedand were without the benefit of IMRT. As IMRT has developed, the use ofhigher MV linac accelerating potential beams and electron beams havebeen largely abandoned by the community. This is partly due to theincreased concern over neutron production (and increased patient wholebody dose) for the increased beam-on times required by IMRT and thecomplexity of optimizing electron beams, but most importantly becauselow MV photon-beam IMRT could produce treatment plans of excellentquality for all sites of cancer treatment.

IMRT represents a culmination of decades of improving 3D dosecalculations and optimization to the point that we have achieved a highdegree of accuracy and precision for static objects. However, there is afundamental flaw in our currently accepted paradigm for dose modeling.The problem lies with the fact that patients are essentially dynamicdeformable objects that we cannot and will not perfectly reposition forfractioned radiotherapy. Even for one dose delivery, intra-fractionorgan motion can cause significant errors. Despite this fact, thedelivery of radiation therapy is traditionally planned on a static modelof radiotherapy targets and critical structures. The real problem liesin the fact that outside of the cranium (i.e., excluding the treatmentof CNS disease using Stereotactic radiotherapy) radiation therapy needsto be fractionated to be effective, i.e., it must be delivered in single1.8 to 2.2 Gy fractions or double 1.2 to 1.5 Gy fractions daily, and istraditionally delivered during the work week (Monday through Friday);taking 7 to 8 weeks to deliver a curative dose of 70 to 72 Gy at 2.0 or1.8 Gy, respectively. This daily fractionation requires the patient andall of their internal organs to be repositioned exactly for accuratedose delivery. This raises an extremely important question for radiationtherapy: “Of what use is all of the elegant dose computation andoptimization we have developed if the targets and critical structuresmove around during the actual therapy?” Recent critical reviews of organmotion studies have summarized the existing literature up to 2001 andhave shown that the two most prevalent types of organ-motion: patientset-up errors and organ motions. While significant physiological changesin the patient do occur, e.g., significant tumor shrinkage inhead-and-neck cancer is often observed clinically, they have not beenwell studied. Organ motion studies have been further subdivided intointer-fraction and intra-fraction organ motion, with the acknowledgementthat the two cannot be explicitly separated, i.e., intra-fractionmotions obviously confound the clean observation of inter-fractionmotions. Data on inter-fraction motion of gynecological tumors,prostate, bladder, and rectum have been published, as well as data onthe intra-fraction movement of the liver, diaphragm, kidneys, pancreas,lung tumors, and prostate. Many peer-reviewed publications, spanning thetwo decades prior to publication have demonstrated the fact that bothinter- and intra-fraction organ motions may have a significant effect onradiation therapy dosimetry. This may be seen in the fact thatdisplacements between 0.5 and 4.0 cm have been commonly observed instudies of less than 50 patients. The mean displacements for manyobservations of an organ motion may be small, but even an infrequent yetlarge displacement may significantly alter the biologically effectivedose received by a patient, as it is well accepted that the correct doseper fraction must be maintained to effect tumor control. In a morefocused review of intra-fraction organ motion recently published byGoitein (Seminar in Radiation Oncology 2004 January; 14(1):2-9), theimportance of dealing with organ motion related dosimetry errors wasconcisely stated: “ . . . it is incontestable that unacceptably, or atleast undesirably, large motions may occur in some patients . . . ” Itwas further explained by Goitein that the problem of organ motions hasalways been a concern in radiation therapy: “We have known that patientsmove and breathe and that their hearts beat and their intestines wrigglesince radiation was first used in cancer therapy. In not-so-distantdecades, our solution was simply to watch all that motion on thesimulator's fluoroscope and then set the field edge wires wide enoughthat the target (never mind that we could not see it) stayed within thefield.”

In an attempt to address the limitations imposed on radiation therapy bypatient setup errors, physiological changes, and organ motion throughoutthe protracted weeks of radiation therapy, the prior art has beenadvanced to imaging systems capable of acquiring a volumetric CT “snapshot” before and after each delivery of radiation. This new combinationof radiation therapy unit with radiology imaging equipment has beentermed image-guided radiation therapy (IGRT), or preferably image guidedIMRT (IGIMRT). The prior art has the potential for removing patientsetup errors, slow physiological changes, and inter-fraction organmotions that occur over the extended course of radiation therapy.However, the prior art cannot account for intra-fraction organ motionwhich is a very significant form of organ motion. The prior art devicesare only being used to shift the gross patient position. The prior artcannot capture intra-fraction organ motion and is limited by the speedat which helical or cone-beam CT imaging may be performed Secondly, butperhaps equally important, CT imaging adds to the ionizing radiationdose delivered to the patient. It is well known that the incidence ofsecondary carcinogenesis occurs in regions of low-to-moderate dose andthe whole body dose will be increased by the application of many CTimage studies.

CT imaging and MRI units were both demonstrated in the 1970's. CTimaging was adopted as the “gold standard” for radiation therapy imagingearly on due to its intrinsic spatial integrity, which comes from thephysical process of X-ray attenuation. Despite the possibility ofspatial distortions occurring in MRI, it is still very attractive as animaging modality for radiotherapy as it has a much better soft tissuecontrast than CT imaging and the ability to image physiological andmetabolic information such as chemical tumor signals or oxygenationlevels. The MRI artifacts that influence the spatial integrity of thedata are related to undesired fluctuations in the magnetic fieldhomogeneity and may be separated into two categories: 1) artifacts dueto the scanner such as field inhomogeneities intrinsic to the magnetdesign and induced eddy currents due to gradient switching; and 2)artifacts due to the imaging subject, i.e., the intrinsic magneticsusceptibility of the patient. Modern MRI units are carefullycharacterized and employ reconstruction algorithms that may effectivelyeliminate artifacts due to the scanner. At high magnetic field strength,in the range of 1.0-3.0 T, magnetic susceptibility of the patient mayproduce significant distortions (which are proportional to fieldstrength) that may often be eliminated by first acquiring susceptibilityimaging data. Recently, many academic centers have started to employ MRIfor radiation therapy treatment planning Rather than dealing withpatient related artifacts at high field, many radiation therapy centershave employed low field MRI units with 0.2-0.3 T for radiation therapytreatment planning, as these units diminish patient-susceptibilityspatial distortions to insignificant levels. For dealing withintra-fraction organ motion MRI is highly favorable due to the fact thatit is fast enough to track patient motions in real-time, has an easilyadjustable and orientable field of view, and does not deliver anyadditional ionizing radiation to the patient which may increase theincidence of secondary carcinogenesis. Breath controlled andspirometer-gated fast multi-slice CT has recently been employed in anattempt to assess or model intra-fraction breathing motion by manyresearch groups. Fast, single-slice MRI has also been employed in theassessment of intra-fraction motions, and dynamic parallel MRI is ableto perform volumetric intra-fraction motion imaging. MRI holds adefinite advantage over CT for fast repetitive imaging due to the needfor CT imaging to deliver increasing doses to the patient. Concerns overincreased secondary carcinogenesis due to whole-body dose already existfor IMRT and become significantly worse with the addition of repeated CTimaging.

In the prior art, two research groups appear to have simultaneously beenattempting to develop a MRI unit integrated with a linac. In 2001, apatent was filed by Green which teaches an integrated MRI and linacdevice. In 2003, a group from the University of Utrecht in theNetherlands presented their design for an integrated MRI and linacdevice and has since reported dosimetric computations to test thefeasibility of their device. The significant difficulty with integratinga MRI unit with a linac as opposed to a CT imaging unit, is that themagnetic field of the MRI unit makes the linac inoperable. It is wellknown that a charged particle moving at a velocity, v, in the presenceof a magnetic field, B, experiences a Lorentz force given by F=q( v× B).The Lorentz force caused by the MRI unit will not allow electrons to beaccelerated by the linac as they cannot travel in a linear path,effectively shutting the linac off. The high radiofrequency (RF)emittance of the linac will also cause problems with the RF transceiversystem of the MRI unit, corrupting the signals required for imagereconstruction and possibly destroying delicate circuitry. Theintegration of a linac with a MRI unit is a monumental engineeringeffort and has not been enabled.

Intensity modulated radiation therapy (IMRT) is a type of external beamtreatment that is able to conform radiation to the size, shape andlocation of a tumor. IMRT is a major improvement as compared toconventional radiation treatment. The radiotherapy delivery method ofIMRT is known in the art of radiation therapy and is described in a bookby Steve Webb entitled “Intensity-Modulated Radiation Therapy” (IOPPublishing, 2001, ISBN 0750306998). This work of Webb is incorporated byreference into the application in its entirety and hereafter referred toas “Webb 2001”. The effectiveness of conventional radiation therapy islimited by imperfect targeting of tumors and insufficient radiationdosing. Because of these limitations, conventional radiation may exposeexcessive amounts of healthy tissue to radiation, thus causing negativeside-effects or complications. With IMRT, the optimal 3D dosedistribution, as defined by criteria known in the art (Webb 2001), isdelivered to the tumor and dose to surrounding healthy tissue isminimized.

In a typical IMRT treatment procedure, the patient undergoes treatmentplanning x-ray CT imaging simulation with the possible addition of MRIsimulation or a position emission tomography (PET) study to obtainmetabolic information for disease targeting. When scanning takes place,the patient is immobilized in a manner consistent with treatment so thatthe imaging is completed with the highest degree of accuracy. Aradiation oncologist or other affiliated health care professionaltypically analyzes these images and determines the 3D regions that needto be treated and 3D regions that need to be spared, such as criticalstructures, e.g. the spinal cord and surrounding organs. Based on thisanalysis, an IMRT treatment plan is developed using large-scaleoptimization.

IMRT relies on two advanced technologies. The first is inverse treatmentplanning Through sophisticated algorithms using high speed computers anacceptable treatment plan is determined using an optimization processwhich is intended to deliver a prescribed uniform dose to the tumorwhile minimizing excessive exposure to surrounding healthy tissue.During inverse planning a large number (e.g. several thousands) ofpencil beams or beamlets which comprise the radiation beam areindependently targeted to the tumor or other target structure with highaccuracy. Through optimization algorithms the non-uniform intensitydistributions of the individual beamlets are determined to attaincertain specific clinical objectives.

The second technology comprising IMRT generally utilizes multi-leafcollimators (MLC). This technology delivers the treatment plan derivedfrom the inverse treatment planning system. A separate optimizationcalled leaf sequencing is used to convert the set of beamlet fluences toan equivalent set of leaf motion instructions or static apertures withassociated fluences. The MLC is typically composed ofcomputer-controlled tungsten leaves that shift to form specificpatterns, blocking the radiation beams according to the intensityprofile from the treatment plan. As an alternative to MLC delivery, anattenuating filter may also be designed to match the fluence ofbeamlets. The current invention contemplates the fact that MLC deliveryis capable of adjusting a delivery rapidly to account for intra-fractionorgan motions while an attenuating filter cannot be actively adjusted.

After the plan is generated and quality control checking has beencompleted, the patient is immobilized and positioned on the treatmentcouch attempting to reproduce the positioning performed for the initialx-ray CT or magnetic resonance imaging. Radiation is then delivered tothe patient via the MLC instructions or attenuation filter. This processis then repeated for many work weeks until the prescribed cumulativedose is assumed to be delivered.

Magnetic resonance imaging (MRI) is an advanced diagnostic imagingprocedure that creates detailed images of internal bodily structureswithout the use of ionizing radiation, which is used in x-ray ormegavoltage x-ray CT imaging. The diagnostic imaging method of MRI isknown in the arts of radiology and radiation therapy and is described inthe books by E. M. Haacke, R. W. Brown, M. R. Thompson, R. Venkatesanentitled Magnetic Resonance Imaging: Physical Principles and SequenceDesign (John Wiley & Sons, 1999, ISBN 0-471-35128-8) and by Z.-P. Liangand P. C. Lauterbur entitled Principles of Magnetic Resonance Imaging: ASignal Processing Perspective. (IEEE Press 2000, ISBN 0-7803-4723-4).These works of Haacke et al. and Liang and Lauterbur are incorporated byreference into the application in their entirety and hereafter referredto as “Haacke et al. 1999” and “Liang and Lauterbur 2001”, respectively.MRI is able to produce detailed images through the use of a powerfulmain magnet, magnetic field gradient system, radiofrequency (RF)transceiver system, and an image reconstruction computer system. OpenMagnetic Resonance Imaging (Open MRI) is an advanced form of MRIdiagnostic imaging that uses a main magnet geometry which does notcompletely enclose the patient during imaging. MRI is a very attractiveimaging modality for radiotherapy as it has a much better soft tissuecontrast than CT imaging and the ability to image physiological andmetabolic information such as spectroscopic chemical tumor signals oroxygenation levels. Many tracer agents exist and are under developmentfor MRI to improve soft tissue contrast (e.g. Gadopentate dimegluminefor kidney or bowel enhancement, or Gadoterate meglumine for generalcontrast). Novel contrast agents are currently under development thatwill allow for the metabolic detection of tumors similar to PET imagingby employing either hyperpolarized liquids containing carbon 13,nitrogen 15, or similar stable isotopic agents or paramagnetic niosomes.All of these diagnostic MRI techniques enhance the accurate targeting ofdisease and help assess response to treatment in radiation therapy.

CT scanning for IMRT treatment planning is performed using thin sections(2-3 mm), sometimes after intravenous injection of an iodine-containingcontrast medium and filmed at soft tissue and bone window and levelsettings. It has the advantage of being more widely available, cheaperthan magnetic resonance imaging (MRI) and it may be calibrated to yieldelectron density information for treatment planning Some patients whocannot be examined by MRI (due to claustrophobia, cardiac pacemaker,aneurism clips, etc.) may be scanned by CT.

The problem of patient setup errors, physiological changes, and organmotions during radiotherapy is currently a topic of great interest andsignificance in the field of radiation oncology. It is well know thatthe accuracy of conformal radiation therapy is significantly limited bychanges in patient mass, location, orientation, articulated geometricconfiguration, and inter-fraction and intra-fraction organ motions (e.g.during respiration), both during a single delivery of dose(intrafraction changes, e.g., organ motions such as rectal distension bygas, bladder filling with urine, or thoracic breathing motion) andbetween daily dose deliveries (interfraction changes, e.g.,physiological changes such as weight gain and tumor growth or shrinkage,and patient geometry changes). With the exception of the subjectinvention, no single effective method is known to account for all ofthese deviations simultaneously during each and every actual dosedelivery. Current state-of-the-art imaging technology allows taking 2Dand 3D megavoltage and orthovoltage x-ray CT “snap-shots” of patientsbefore and after radiation delivery or may take time resolved 2Dradiographs which have no soft tissue contrast during radiationdelivery.

Great advances have been made in conformal radiation therapy; however,their true efficacy is not realized without complete real-time imagingguidance and control provided by the present invention. By the term“real-time imaging” we mean repetitive imaging that may be acquired fastenough to capture and resolve any intra-fraction organ motions thatoccur and result in significant changes in patient geometry while thedose from the radiation beams are being delivered. The data obtained byreal-time imaging allows for the determination of the actual dosedeposition in the patient. This is achieved by applying known techniquesof deformable registration and interpolation to sum the doses deliveredto the moving tissues and targets. This data taken over the entiremulti-week course of radiotherapy, while the radiation beams arestriking the patient and delivering the dose, allows for thequantitative determination of 3D in vivo dosimetry. Hence, the presentinvention enables the only effective means of assessing and controllingor eliminating organ motion related dose delivery errors.

SUMMARY OF THE INVENTION

The present invention provides a radiation treatment system including:at least one though possibly more radioisotopic sources to produceionizing radiation treatment beams, at least one though possibly moreMLC or attenuator systems to perform IMRT with the treatment beams; amagnetic resonance imaging (MRI) system that images the target regionand surrounding healthy tissue or critical structures simultaneouslyduring delivery of the ionizing radiation; and/or a controllercommunicably connected to all components. The image data derived fromthe MRI allows for the quantitative assessment of the actual deliveredionizing radiation dose and the ability to reoptimize or replan thetreatment delivery to guide the ionizing radiation delivered by IMRT tothe target region more accurately. We now describe a beneficialembodiment of the invention. In this beneficial embodiment, the mainmagnet Helmholtz coil pair of an open MRI is designed as a splitsolenoid so that the patient couch runs through a cylindrical bore inthe middle of the magnets and the IMRT unit is aimed down the gapbetween the two selonoidal sections at the patient (FIG. 1 through FIG.4). In this embodiment, the split solenoidal MRI (015) remainsstationary while the shielded co-registered isotopic radiation sourcewith a multi-leaf collimator IMRT unit (020) is rotated axially aroundthe couch on the gantry (025) (note more than one (020) could bebeneficially employed). The patient (035) is positioned on the patientcouch (030) for simultaneous imaging and treatment. The co-registeredisotopic radiation source (020) with a multi-leaf collimator contains aradioisotopic source (115) which is collimated with a fixed primarycollimator (120), a secondary doubly divergent multileaf collimator(125), and tertiary multi-leaf collimator (130) to block interleafleakage from the secondary multi-leaf collimator (125) (FIG. 5 throughFIG. 7).

This embodiment is beneficial as it removes the need for rotating theopen MRI to provide axial treatment beam access and it provides amagnetic field along the patient in the cranial-caudal direction,allowing for improved MRI speed using parallel multi-phased array RFtransceiver coils for fast image acquisition.

We now describe additional beneficial embodiments of the process of thisinvention with varying complexity and computational demands. All ofthese process embodiments could employ any device embodiment. All suchprocess embodiments may include the step of acquiring high resolutiondiagnostic quality volumetric MRI data before the daily delivery ofradiation and then acquiring real-time MRI data during the radiationdelivery where the real-time data may be collected on a differentspatial grid or with a diminished signal-to-noise ratio to improve thespeed of acquisition. One beneficial process embodiment would take theMRI data and apply methods known in the art for deformable imageregistration and dose calculation to the delivered IMRT cobalt unitfluences to determine the dose delivered to the target and criticalstructures during each delivery fraction. Corrections to the patient'streatment could then be taken to add or subtract delivery fractions toimprove tumor control or reduce side effects, respectively. Along withthe dosimetric assessment, the size and progression of the patient'sdisease would also be assessed on a daily basis.

A second beneficial process embodiment would take the MRI data andperform a reoptimization of the IMRT treatment plan before each singleradiation delivery to improve the accuracy of the treatment delivery.This process would be combined with the previous process to assess thedose delivered to the target and critical structures during eachdelivery fraction.

A third beneficial process embodiment would take the MRI data andperform a reoptimization of the IMRT treatment plan on a beam-by-beambasis before the delivery of each radiation beam in a single radiationdelivery to improve the accuracy of the treatment delivery. This processgenerally includes that the first process to be performed rapidly beforeeach beam delivery.

A fourth beneficial process embodiment would take the MRI data andperform reoptimization of the IMRT treatment plan on a moment-by-momentbasis during the delivery of each part of each radiation beam in asingle radiation delivery to improve the accuracy of the treatmentdelivery. This process includes that the first process to be performedin real-time substantially simultaneously with the radiation delivery.The present invention contemplates the use of parallel computationemploying many computers beneficially connected via a low latency localnetwork or a secure connection on a wide area network may be used togreatly enhance the speed of the algorithms known in the art for MRIimage reconstruction, deformable image registration, dose computation,and IMRT optimization.

In another aspect, the present invention also provides a method ofapplying radiotherapy, having the steps of determining a treatment planfor applying radiotherapy; obtaining images of a target region within avolume of a subject using a magnetic resonance imaging (MRI) system;irradiating the target and critical structure regions with a treatmentbeam, wherein the treatment beam treats the target region; andcontinuing to obtain images of the target and critical structure regionsduring irradiation of the target region; wherein the treatment plan maybe altered during treatment based upon images of the target and criticalstructure regions obtained during treatment.

BRIEF DESCRIPTION OF DRAWINGS

There are shown in the drawings, embodiments which are presentlycontemplated, it being understood, however, that the invention is notlimited to the precise arrangements and instrumentalities shown.

FIG. 1 is a schematic of a radiation therapy system including an opensplit solenoidal magnetic resonance imaging device (015), a shieldedco-registered isotopic radiation source with a multi-leaf collimator(020) (note that more than one 020 could be applied in a beneficialembodiment), a gantry (025) for changing the angle of (020), a patientcouch (030), and a patient (035) in position for simultaneous imagingand treatment.

FIG. 2 is a demonstration of gantry rotation, where the shieldedco-registered isotopic radiation source with a multi-leaf collimator(020), has been rotated from a right lateral beam position to ananterior-posterior beam position.

FIG. 3 is a top view of the system in FIG. 1.

FIG. 4 is a side view of the system in FIG. 1.

FIG. 5 is a detailed schematic of the co-registered isotopic radiationsource with a multi-leaf collimator shown as (020) in FIG. 1. Aradioisotopic source (115), is shown with a fixed primary collimator(120), a secondary doubly divergent multileaf collimator (125), andtertiary multi-leaf collimator (130) to block interleaf leakage from thesecondary multi-leaf collimator (125).

FIG. 6 is a perspective view of the secondary doubly divergentmulti-leaf collimator (125), and the tertiary multi-leaf collimator(130) to block interleaf leakage from the secondary multi-leafcollimator (125).

FIG. 7 is a beams-eye view of the radioisotopic source (115), thesecondary doubly divergent multi-leaf collimator (125), and the tertiarymulti-leaf collimator (130) to block interleaf leakage from thesecondary multi-leaf collimator (125).

FIG. 8 displays axial dose distributions from the single head-and-neckIMRT case planned using the commissioned cobalt beamlets.

FIG. 9 displays the DVH data derived from the single head-and-neck IMRTcase planned using the commissioned cobalt beamlets.

FIG. 10 cobalt beamlets dose distributions in water with and without a0.3 Tesla magnetic field.

FIG. 11 cobalt beamlets dose distributions in water and lung with andwithout a 0.3 Tesla magnetic field.

FIG. 12 cobalt beamlets dose distributions in water and air with andwithout a 0.3 Tesla magnetic field.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is more particularly described in the followingexamples that are intended to be illustrative only since numerousmodifications and variations therein will be apparent to those skilledin the art. As used in the specification and in the claims, the singularform “a,” “an,” and “the” may include plural referents unless thecontext clearly dictates otherwise. Also, as used in the specificationand in the claims, the term “comprising” may include the embodiments“consisting of and “consisting essentially of.”

The invention is both a device and a process for performing hightemporal- and spatial-resolution magnetic resonance imaging (MRI) of theanatomy and disease of a patient during intensity modulated radiationtherapy (IMRT) to directly measure and control the highly conformalionizing radiation dose delivered to the patient. In a beneficialembodiment, this invention combines the technologies of an open MRI thatallows for axial access with IMRT radiation beams to the patient, amultileaf-collimator or compensating filter-based IMRT delivery system,and cobalt-60 teletherapy radiation source or sources into a singleco-registered and gantry mounted system.

As mentioned, the prior art does not simultaneously image the internalsoft tissue anatomy of a person in real-time during the delivery ofradiation therapy while the beams are striking the patient. Rather, animage is generated prior to and/or after the radiation delivery, andthese images do not reflect any movement and/or natural changes that mayoccur in the patient during radiation delivery. As such, targetedradiation without the invention described here may not be successful if,after taking an initial image, the portion of the body to be treatedeither changes in size naturally, or changes in location due to theshifting of the patient prior to treatment; i.e., the occurrence ofpatient setup errors or errors in the geometry and alignment of thepatients anatomy; physiological changes in the patient, such as weightloss or tumor growth and shrinkage; and organ motions in the patientincluding but not limited to breathing motion, cardiac motion, rectaldistension, peristalsis, bladder filling, and voluntary muscular motion.

The present invention helps to eliminate all of these problems byperforming real-time MRI of the patient substantially simultaneous toradiation delivery, and then readjusting the targeted radiation if theregion to be treated suffers from any type of dosimetric error causedpatient setup error, physiological change, and inter-fraction orintra-fraction organ motion. Many actions may be taken including, butnot limited to: shifting the patient position to account for changes insize and/or position of targets and anatomy; stopping treatmentaltogether to permit additional calculations to be determined beforerestarting treatment or allow for the cessation of transitory motion;adding extra delivery fractions to increase the probability of tumorcontrol or limiting the number of delivery fractions to decrease theprobability of side effect; any of the beneficial process embodimentsprevious described; and reoptimizing the IMRT treatment plan on avariety of time scales, e.g., reoptimization for every delivery, everybeam, or every segment in the IMRT plan is performed.

A beneficial embodiment of the present invention includes a computercontrolled cone-beam cobalt therapy unit, such as a cobalt-60 therapyunit, equipped with a multileaf collimator or an automated compensatingfilter system mounted on a rotational gantry along with an orthogonallymounted “Open” MRI unit. As seen in FIG. 1, the IMRT cobalt unit (020)projects its cone-beam geometry radiation down the center of the openingof the axial open MRI unit (015) and the IMRT cobalt unit rotatesaxially (about the longitudinal (cranial-caudal) axis of the patient)about the patient on a gantry (025). An adjustable treatment couch (030)may be used to support the patient in a stationary position while thegantry rotates to change the beam angle.

The present invention uses cobalt teletherapy as the radiation therapy.While some IMRT uses a linear electron accelerator for delivering a morepenetrating radiation therapy, the accelerator itself produces atreatment beam that is highly variable in regards to the level ofradiation emitted. As such, it becomes difficult to accurately determinethe amount of radiation that is being used on the patient and tocoordinate the motion of an MLC for IMRT delivery. Gamma-rays areelectromagnetic radiation emitted by the disintegration of a radioactiveisotope and have enough energy to produce ionization in matter,typically from about 100 keV to well over 1 MeV. The most usefulgamma-emitting radioactive isotopes for radiological purposes are foundto be cobalt (Co 60), iridium (Ir 192), cesium (Cs 137), ytterbium (Yb169), and thulium (Tm 170). As such, the disintegration of a radioactiveisotope is a well-known phenomena and, therefore, the radiation emittedby cobalt teletherapy is more consistent and, therefore, easier tocalculate in terms of preparing a treatment regimen for a patient.

Enablement of the present invention's cobalt IMRT has been demonstratedvia computational analysis. Simulations have been performed of IMRTdelivery with a commercially available cobalt therapy unit and a MLC. A3D image-based radiation therapy treatment planning system with a cobaltbeamlet model was commissioned and validated using measured radiochromicfilm data from a Theratronics 1000C cobalt therapy unit. An isotropic4×4×4 mm³ dose voxel grid (effectively Shannon-Nyquist limited for γ-rayIMRT source penumbra) was generated. This beamlet model was fitted topublished data and validated with radiochromic film measurements of 1×1cm² beamlets formed by a Cerrobend block and measured using a previouslyreported methodology. The calculation depths were then determined forthe same voxels with standard three-dimensional ray-tracing of thestructures. Density scaling to the depths computed was used to betteraccount for tissue heterogeneities in the dose model. The CPLEX, ILOGConcert Technologies industrial optimization solver using animplementation of the barrier interior-point method with dense columnhandling for IMRT optimization was used to solve for optimal IMRT plans.Beamlet fluences were discretized for each beam angle to 5% levels forleaf sequencing. The resulting plan dose distribution and histogramswere computed by summing the dose values weighted by the deliverablediscretized intensities. Leaf-transmission leakage intensities wereconservatively estimated at 1.7% for otherwise zero intensity beamlets.Finally, standard methods of heuristic leaf-sequencing optimization tocreate delivery instructions for the treatment plans were employed. Weadopted the Virginia Medical College simultaneous integrated boost (SIB)target dose-level scheme as it is the largest maximum to minimumclinical prescription dose ratio advocated in the literature, making itthe most difficult dose prescription scheme to satisfy. Head-and-neckIMRT provides an excellent basis for testing IMRT optimization forseveral reasons: 1) there are well defined treatment goals of sparingsalivary glands and other structures while maintaining homogeneoustarget coverage; 2) attempting to achieve these goals tests IMRToptimization to its technical limits; and 3) a large phase I/IImulti-institutional trial, the Radiation Therapy Oncology Group (RTOG)'sH-0022 Phase I/II Study of Conformal and Intensity Modulated Irradiationfor Oropharyngeal Cancer, has defined a common set of planning criteria.The case examined was run with 7 equispaced beams having InternationalElectrotechnical Commission (IEC) gantry angles of 0°, 51°, 103°, 154°,206°, 257°, and 309°. The treatment planning system generated 1,289beamlets to adequately cover the targets from the seven beam angles, andthe 4 mm isotropic voxel grid generated 417,560 voxels. Results areshown in FIG. 8 and FIG. 9. Note that our system normalized plans toensure 95% coverage of the high dose target. FIG. 8 displays axial dosedistributions from the single head-and-neck IMRT case planned using thecommissioned cobalt beamlets. Excellent target coverage and tissuesparing may be observed. FIG. 9 displays the DVH data derived from theleaf sequenced and leakage corrected plan (i.e., deliverable plan) usingthe 4 mm voxels and 1 Gy dose bins. The cobalt source based IMRT createdan excellent IMRT treatment plan for a head-and-neck patient. The γ-rayIMRT was able to clearly spare the right parotid gland (RPG) and keepthe left parotid (LPG) and right submandibular glands (RSMG) under 50%volume at 30 Gy, while covering more than 95% of the target volumes (CTVand GTV) with the prescription dose or higher. All other structures werebelow tolerance. The unspecified tissue (SKIN) was kept below 60 Gy,with less than 3% of the volume above 50 Gy. The optimization model usedwas the same as published in Romeijn et al. and was not modified for thecobalt beams. For sites with larger depths such as prostate and lung itis known in the art that the addition of extra beams or isocentersallows for the creation of treatment plans using cobalt IMRT that mayachieve the same clinical quality criteria as linac-based IMRT. Thisenabling demonstration shows that a cobalt therapy unit is capable ofproviding high quality IMRT.

Enablement of the present invention's dose computation for cobalt IMRTin the presence of the magnetic field has been demonstrated viacomputational analysis. In addition, by using cobalt teletherapy, thepresent invention is better able to make calculations based upon themagnetic field of the MRI. When the radiation therapy is performed whilethe patient is stationed within the MRI, the magnetic field will cause aslight deflection of the targeted radiation. As such, the calculationsused to determine the treatment regimen need to take this deflectioninto account. A charged particle moving in a vacuum at a velocity, v, inthe presence of a magnetic field, B, experiences a Lorentz force givenby F=q( v× B). This force is not significant enough to significantlychange the physics of the interactions of ionizing photons and electronswith matter; however, it may influence the overall transport of ionizingelectrons and hence the resulting dose distribution. The impact ofmagnetic fields on the transport of secondary electrons has been wellstudied in the physics literature, starting more than 50 years ago.Recent studies have employed Monte Carlo simulation and analyticanalysis in an attempt to use a localized magnetic field to help focusor trap primary or secondary electrons to increase the local dosedeposition in the patient. All of these studies have examined aligningthe direction of the magnetic field lines along the direction of thebeam axis to laterally confine the electron transport with the Lorentzforce (called “longitudinal” magnetic fields, where the termlongitudinal refers to the beam and not the patient). For high fieldMRI, with magnetic fields between about 1.5-3.0 T is known that theinitial radius of gyration is small with respect to the MFP oflarge-angle scattering interactions for the secondary electrons(bremsstrahlung, elastic scatter, and hard collisions) and thiscondition results in the desired trapping or focusing of the electrons.As the electrons lose energy the radius decreases as it is proportionalto | v| and, in the absence of large-angle scattering interactions(CSDA) the electrons would follow a spiral with decreasing radius untilthey stop. Although this spiraling may change the fluence of electronsit is known that it does not produce any significant synchrotronradiation. In the present invention, the magnetic field must beorthogonal to the radiation beams in order allow parallel MRI forreal-time imaging. Recent work has shown that a 1.5 T magnetic fieldperpendicular to the beam axis of a 6 MV linac beam may significantlyperturb the dose distribution to water for a 6 MV linac beamlet. Both toavoid such dose distribution distortions and to prevent MRI artifactsthat could compromise the spatial integrity of the imaging data, abeneficial embodiment of the present invention uses a low field open MRIdesign that allows the magnetic field to be directed along thesuperior-inferior direction of the patient (see FIG. 1). Simpleestimates of the radii of gyration for secondary electrons from cobalt γrays indicate that the radii of gyration are much greater than the MFPfor large-angle scattering interactions for electrons. This is easilyunderstood as the Lorentz force is proportional to the magnitude of themagnetic field, | B| and the radius of gyration is inverselyproportional to the magnetic field (104). We have pursued modeling abeamlet from a cobalt γ-ray source in a slab phantom geometry using thewell-validated Integrated Tiger Series (ITS) Monte Carlo package and itsACCEPTM subroutine for transport in magnetic fields. For the simulationswe employed 0.1 MeV electron and 0.01 MeV photon transport energycutoffs, the standard condensed history energy grid (ETRAN approach),energy straggling sampled from Landau distributions, mass-collisionalstopping powers based on Bethe theory, default electron transportsubstep sizes, and incoherent scattering including binding effect. Threepairs of simulations were run where each pair included the run with andwithout a 0.3 T uniform magnetic field parallel to the beam direction. A2 cm circular cobalt γ-ray beamlet was modeled on the followinggeometries: a 30×30×30 cm³ water phantom; a 30×30×30 cm³ water phantomwith a 10 cm lung density (0.2 g/cc) water slab at 5 cm depth; and a30×30×30 cm³ water phantom with a 10 cm air density (0.002 g/cc) waterslab at 5 cm depth. Simulations were run with between 30 and 100 millionhistories on a P4 1.7 GHz PC for between 8 and 30 hours to obtain lessthan a percent standard deviation in the estimated doses. The resultsare displayed in FIGS. 10-12. FIG. 10 clearly demonstrates that a 0.3 Tperpendicular uniform magnetic field, as would exist in a beneficialembodiment of the current invention will not measurably perturb the dosedistribution in soft tissue or bone. A very useful treatment site forthe present invention will be lung and thorax which contains the mostsignificant tissue heterogeneities in the body. As seen in FIG. 11,adding a 12 cm lung density (0.2 g/cc) water slab to the phantom causesa very small yet detectable perturbation in the dose at the interfacesof the high and low density regions. These perturbations are smallenough to allow acceptable clinical application without correction. InFIG. 12, we finally observe significant perturbations, which existlargely in the low-density and interface regions. This demonstrates thatair cavities will hold the greatest challenge for accurate dosimetry.However, other than at interfaces with lower density media there shouldbe no significant perturbations in soft tissue and bone (where the MFPshortens even more than soft tissue). This data demonstrates that in abeneficial embodiment of the present invention with a low (0.2-0.5Tesla) field MRI, dose perturbation will be small except inside of aircavities were accurate dosimetry is not required due to an absence oftissue. By using a known radiation source, such as a cobalt teletherapyunit, the amount of deflection may be easily determined if the strengthof the MRI field is known. However, even if the strength of the field isknown, if a linear accelerator is used, the unknown energy spectrum ofthe radiation makes the calculations much more difficult.

Alternate sources of radiation that do not interfere significantly withthe operations of the MRI unit such as protons, heavy ions, and neutronsthat are produced by an accelerator or reactor away from the MRI unitand transported by beam to patient are also included in the invention.

In addition, the strength of the MRI field will factor into thecalculations and, as a result, the use of open MRIs offers advantagesover closed MRIs. In an open MRI, the strength of the field generated isgenerally less than the field of a closed MRI. As such, the imagesresulting from an open MRI have more noise and are not as clear and/ordefined as images from a higher field closed MRI. However, the strongerfield of the closed MRI causes more of a deflection of the radiationtreatment than the weaker field of an open MRI. Accordingly, dependingon the characteristics most beneficial to a given treatment regimen, thepresent invention contemplates that a closed MRI could be used. However,due to ease of calculation and/or the fact that a slightly less clearimage during treatment is sufficient for adjusting most treatmentregimens, the present invention contemplates that an open MRI of thegeometry shown in FIG. 1, is used with the cobalt teletherapy toeliminate significant dose perturbations, prevent spatial imagingdistortions, and allow for fast parallel phased array MRI.

By using an open MRI and cobalt teletherapy, the present inventionprovides three dimensional (3D) imaging of a patient during theradiation therapy. As such, by using the 3D images of the target regionand the planning images of the target region a displacement isdetermined which is updated based upon the continuous 3D images receivedduring the radiotherapy process. Using the information obtained, thepatient may then be then translated relative to the treatment beam toreduce the displacement during the irradiation process, such as if themeasured displacement is outside a predetermined limit. Irradiation maythen continue after translation. Alternatively, the treatment beam maybe moved. The translation may occur during treatment or treatment may bestopped and then translation may occur.

By using 3D images during treatment and using these images to rapidlyposition and/or adjust the patient during the radiotherapy process,treatment accuracy may be substantially improved. If the patient becomesmisaligned while radiation is being applied, the misalignment may bemitigated through positional adjustment. In addition to possible doseescalation, improved positional accuracy permits treatment of tumorsthat are currently considered not treatable with radiation usingconventional systems. For example, primary spinal cord tumors and spinalcord metastases are typically not treated by conventional radiationsystems due to the high accuracy needed to treat lesions in suchimportant functional anatomic regions. The increased precision providedby 3D imaging during treatment makes it feasible to treat these types oftumors. Improvements are also expected for targets located in the lung,upper thorax, and other regions where intra-fraction organ motions areknown to cause problems with radiotherapy dosimetry.

In an alternative embodiment, the present invention may include aseparate guidance system to track the patient location that may be usedto correlate the actual patient position with the imaging informationobtained during both planning and radiotherapy. This portion of theinvention may significantly improve the ease of patient positioning byproviding updateable image correlation and positioning informationthroughout the patient set-up and treatment delivery phases, even whenthe patient is moved to positions that are not perpendicular to thecoordinate system of the therapy machine. This ability to monitorpatient position at non-coplanar treatment positions may be asignificant improvement over conventional radiotherapy systems. In onebeneficial embodiment, the guidance system may include an adjustable bedor couch for the patient to be placed upon. In an alternative beneficialembodiment, the guidance system may include a gantry that permitssubstantially simultaneous movement of the MRI and the cobalt therapyunit. Some beneficial embodiments include both the gantry and theadjustable bed or couch.

The present invention determines the initial radiation treatment and/orany changes to the treatment regimen based upon the use of a computerprogram that takes into account various factors including, but notlimited to, the area of the patient to be treated, the strength of theradiation, the strength of the MRI field, the position of the patientrelative to the radiation unit, any change in the patient duringtreatment, and/or any positional changes necessary of the patient and/orthe radiation unit during treatment. The resulting IMRT is thenprogrammed and the treatment is started.

One embodiment for determining a treatment plan for intensity modulatedradiation treatment (IMRT) as used in the present invention includes thesteps of dividing a three dimensional volume of a patient into a grid ofdose voxels, wherein each dose voxel is to receive a prescribed dose ofradiation from a plurality of beamlets each having a beamlet intensity;and providing a convex programming model with a convex objectivefunction to optimize radiation delivery. The model is solved to obtain aglobally optimal fluence map, the fluence map including beamletintensities for each of the plurality of beamlets. This method isdescribed in greater detail in related application U.F. Disclosure No.11296.

In general, the method used for determining a treatment plan, in onebeneficial embodiment, is the interior point method and variantsthereof. This method is beneficial due to its high efficiency andresulting generally short computational times. The interior point methodis described in a book by Steven J. Wright entitled “Primal-DualInterior-Point Methods” (SIAM, Publications, 1997, ISBN 089871382X).Primal-dual algorithms have emerged as the most beneficial and usefulalgorithms from the interior-point class. Wright discloses the majorprimal-dual algorithms for linear programming, including path-followingalgorithms (short- and long-step, predictor-corrector),potential-reduction algorithms, and infeasible-interior-pointalgorithms.

Once the treatment plan is determined, the present invention enables theclinician to ensure that the treatment plan is followed. The patient tobe treated is placed in the MRI. An image of the area to be treated istaken and the MRI continues to transmit a 3D image of the area. Thetreatment plan is input into the cobalt radiation teletherapy unit andtreatment commences. During treatment, a continuous image of the areabeing treated is observed. If the location of the area to be treatedchanges, such as if the patient moves or the area to be treated changesin size, the present invention either recalculates the treatment planand/or adjusts the patient or radiation unit without interruptingtreatment; or the present invention stops treatment, recalculates thetreatment plan, adjusts the patient and/or adjusts the radiation unitbefore recommencing treatment.

The present invention contemplates multiple process embodiments that maybe used in improving the accuracy of the patient's therapy. One processembodiment would take the MRI data and apply methods known in the artfor deformable image registration and dose calculation to the deliveredIMRT cobalt unit fluences to determine the dose delivered to the targetand critical structures during each delivery fraction. Corrections tothe patient's treatment could then be taken to add or subtract deliveryfractions to improve tumor control or reduce side effects, respectively.Along with the dosimetric assessment, the size and progression of thepatient's disease would also be assessed on a daily basis.

A second process embodiment would take the MRI data and perform areoptimization of the IMRT treatment plan before each single radiationdelivery to improve the accuracy of the treatment delivery. This processwould be combined with the previous process to assess the dose deliveredto the target and critical structures during each delivery fraction.

A third process embodiment would take the MRI data and perform areoptimization of the IMRT treatment plan on a beam-by-beam basis beforethe delivery of each radiation beam in a single radiation delivery toimprove the accuracy of the treatment delivery. This process includesthat the first process be performed rapidly before each beam delivery.

A fourth process embodiment would take the MRI data and performreoptimization of the IMRT treatment plan on a moment-by-moment basisduring the delivery of each part of each radiation beam in a singleradiation delivery to improve the accuracy of the treatment delivery.This process also includes that the first process be performed inreal-time simultaneously with the radiation delivery. The presentinvention contemplates the use of parallel computation employing manycomputers beneficially connected via a low latency local network or asecure connection on a wide area network may be used to greatly enhancethe speed of the algorithms known in the art for MRI imagereconstruction, deformable image registration, dose computation, andIMRT optimization.

Reference is now made with specific detail to the drawings in which likereference numerals designate like or equivalent elements throughout theseveral views, and initially to FIG. 1.

In FIG. 1, the present invention, in one embodiment, shows the system ofthe present invention and having an open MRI 015 and an IMRT cobalttherapy unit 020. The system also includes a means to perform IMRT in020, such as an MLC or compensation filter unit, and a gantry 025 thatmay be used for cobalt unit 020 rotation while keeping the MRI 015stationary. The patient 035 is positioned in the system on anadjustable, stationary couch 030.

FIG. 2 shows the system in use and wherein the gantry 025 has beenrotated approximately 90 degrees clockwise. As such, the cobalt therapyunit 020 is in position to treat the patient 035 in one of many selectedlocations. FIG. 3 is a top view of the system in FIG. 1. FIG. 4 is aside view of the system in FIG. 1.

Although the illustrative embodiments of the present disclosure havebeen described herein with reference to the accompanying drawings andexamples, it is to be understood that the disclosure is not limited tothose precise embodiments, and various other changes and modificationsmay be affected therein by one skilled in the art without departing fromthe scope of spirit of the disclosure. All such changes andmodifications are intended to be included within the scope of thedisclosure as defined by the appended claims.

1. A radiation treatment system, comprising: an irradiating deviceconfigured to deliver ionizing radiation to a subject from one or moretreatment beams selected from the group of radioisotope beams, protonbeams and heavy ion beams; a magnetic resonance imaging system operablyengaged with the irradiating device, the magnetic resonance imagingsystem configured to acquire a sequence of 3D images of the subject fastenough to capture intra-fraction organ motions; a controller incommunication with the irradiating device and the magnetic resonanceimaging system and configured to substantially simultaneously a) controlthe magnetic resonance imaging system to acquire the 3D images of thesubject; and b) control the irradiating device to deliver ionizingradiation to the subject and record delivered treatment beam fluences;and c) determine an actual dose deposition in the subject from the 3Dimages of the subject and the delivered treatment beam fluences.
 2. Theradiation treatment system according to claim 1 wherein a magneticresonance imaging system magnetic field is substantially orthogonal tothe one or more treatment beams.
 3. The radiation treatment system ofclaim 2 further comprising a multi-leaf collimator configured to rapidlyadjust radiation delivery to account for intra-fraction organ motions.4. The radiation treatment system of claim 3, wherein the multi-leafcollimator comprises a fixed primary collimator, a secondary doublydivergent multileaf collimator, and a tertiary multi-leaf collimatorconfigured to block interleaf leakage from the secondary multi-leafcollimator.
 5. The radiation treatment system of claim 2, wherein thecontroller is configured to employ deformable image registration indetermining the actual dose deposition in the subject.
 6. The radiationtreatment system of claim 2 wherein the controller is configured todeliver the ionizing radiation to the subject through intensitymodulated radiation therapy.
 7. The radiation treatment system of claim6 wherein the controller is configured to reoptimize the delivery ofionizing radiation to the subject based on the determined actual dosedeposition.
 8. The radiation treatment system of claim 6 wherein thecontroller is configured to deliver of ionizing radiation to the subjectbased on a treatment plan.
 9. The radiation treatment system of claim 8wherein the controller is configured to alter the treatment plan basedon the actual dose deposition.
 10. The radiation treatment system ofclaim 2 wherein the controller is configured to stop the delivery ofionizing radiation to the subject if the actual dose depositionevidences a dosimetric error.
 11. The radiation treatment system ofclaim 2, wherein the magnetic resonance imaging system is furtherconfigured to acquire magnetic resonance imaging data that identifiesregions of tracer uptake substantially simultaneously to the delivery ofionizing radiation to the subject.
 12. The radiation treatment system ofclaim 2, wherein the magnetic resonance imaging system is furtherconfigured to acquire magnetic resonance imaging data that identifiesregions of contrast enhancement substantially simultaneously to thedelivery of ionizing radiation to the subject.
 13. The radiationtreatment system of claim 2, wherein the magnetic resonance imagingsystem is further configured to acquire spectroscopic informationsubstantially simultaneously to the delivery of ionizing radiation tothe subject.
 14. The radiation treatment system of claim 2, wherein themagnetic resonance imaging system is further configured to acquire oneor more types of information selected from the group of metabolicinformation and physiological information substantially simultaneouslyto the delivery of ionizing radiation to the subject.
 15. The radiationtreatment system of claim 2, wherein the magnetic resonance imagingsystem is further configured to acquire one or more types of informationselected from the group of magnetic resonance angiography data andlymphangiography data substantially simultaneously to the delivery ofionizing radiation to the subject.
 16. The radiation treatment system ofclaim 2, wherein the magnetic resonance imaging system is furtherconfigured to perform in vivo thermometry.
 17. The radiation treatmentsystem of claim 2, wherein the system is further configured to performablative therapy under substantially simultaneous image guidance.
 18. Amethod of radiation treatment comprising: delivering ionizing radiationto a subject with an irradiating device including one or more treatmentbeams selected from the group of radioisotope beams, proton beams andheavy ion beams; acquiring, with a magnetic resonance imaging systemoperably engaged with the irradiating device, a sequence of 3D images ofthe subject fast enough to capture intra-fraction organ motions;controlling the magnetic resonance imaging system to acquire the 3Dimages of the subject and, substantially simultaneously, controlling theirradiating device to deliver ionizing radiation to the subject; and,recording delivered treatment beam fluences; and determining an actualdose deposition in the subject from the 3D images of the subject and thedelivered treatment beam fluences.
 19. The method of radiation treatmentof claim 18 wherein the delivering of ionizing radiation is performedwith the one or more treatment beams being substantially orthogonal to amagnetic resonance imaging system magnetic field.
 20. The method ofradiation treatment of claim 18 further comprising rapidly adjustingradiation delivery with a multi-leaf collimator to account forintra-fraction organ motions.
 21. The method of radiation treatment ofclaim 18 wherein determining the actual dose deposition furthercomprises the use of deformable image registration.
 22. The method ofradiation treatment of claim 18 wherein delivering ionizing radiationfurther comprises intensity modulated radiation therapy.
 23. The methodof radiation treatment of claim 18 further comprising reoptimizing thedelivery of ionizing radiation to the subject based on the determinedactual dose deposition
 24. The method of radiation treatment of claim 18wherein the delivering of ionizing radiation to the subject is based ona treatment plan.
 25. The method of radiation treatment of claim 24further comprising altering the treatment plan based on the actual dosedeposition.
 26. The method of radiation treatment of claim 18 furthercomprising stopping the delivery of ionizing radiation to the subject ifthe actual dose deposition evidences a dosimetric error.